The overall objective, of this proposal, is to determine if there is a link between the use of antibiotics in food animals and the presence of resistant Salmonella in the human population. The hypothesis is that the therapeutic use of ceftiofur in food animals is selecting for resistance to cephalosporins in members of the Family Enterobacteriaceae. Therefore, our short-term goal is to determine if the use of ceftiofur in sick cattle has resulted in resistant zoonotic salmonellosis in people. Our intention is to investigate the source of ceftiofur/ceftriaxone-resistant isolates cultured in our State Veterinary Diagnostic Laboratory and determine if they are related to ceftriaxone resistant cases of salmonellosis in humans identified by the Public Health Service in Georgia and the Centers for Disease Control. [unreadable] [unreadable] Specific aim 1. Determine whether ceftriaxone-resistant Salmonella isolates identified by our diagnostic laboratory are genetically related to human isolates associated with outbreak or sporadic cases of salmonellosis. The working hypothesis will be tested by determining the genetic relatedness of ceftriaxone-resistant Salmonella from farms and human cases by PFGE and characterizing the cephalosporinase locus using molecular techniques. [unreadable] [unreadable] Specific aim 2. Determine the prevalence of ceftiofur resistance in the normal, gram negative flora of food production animals and potential transmission of ceftriaxone resistance from animal microflora to Salmonella Ceftiofur usage may amplify the gene reservoir by enriching for normal flora containing extended-spectrum cephalosporinases. The working hypothesis will be tested through molecular analysis of cephalosporinase(s) within animal microflora gathered from farms with or without a history of ceftiofur usage. We will also address the potential for plasmid transmission of ceftriaxone resistance to Salmonella from the animals' microflora in vitro as well as with a simulated animal production environment. By surveying the animals on the farm, we will discern whether antibiotic use on the farm influences the acquisition of drug resistance by Salmonella interacting with the resident microflora of cattle. This proposal seeks to involve undergraduate students in molecular epidemiology investigations to increase their exposure to biomedical research. [unreadable] [unreadable]